Microvascular in vivo assessment of reperfusion injury: significance of prostaglandin E1 and I2 in postischemic 'no-reflow' and 'reflow-paradox'

Microvascular ischemia-reperfusion (I/R) injury is characterized by failure of capillary perfusion ("no-reflow") and reoxygenation-associated phenomena ("reflow-paradox"), including activation of leukocyte-endothelium interaction with cytotoxic mediator-induced loss of endothelial integrity. The objectives of this study were to elucidate the impact of both prostaglandins E(1) (PGE(1)) and I(2) (PGI(2)) in microvascular reperfusion injury, with special focus on the distinct pathophysiology of no-reflow- and reflow-paradox phenomena.By use of the hamster dorsal skinfold preparation and in vivo fluorescence microscopy, the microcirculation of a striated skin muscle was assessed before 4 h of pressure-induced ischemia and 0.5, 2, and 24 h after onset of reperfusion.I/R was characterized by enhanced leukocyte-endothelium interaction in postcapillary venules, increase of macromolecular leakage, and reduction of functional capillary perfusion (P0.05). Intravenous 2-h infusion of PGE(1), starting with onset of reperfusion, reduced leukocyte adhesion and macromolecular leakage in postcapillary venules during early reperfusion (P0.05), while 6-h infusion, given during ischemia and early reperfusion, showed no significant effects. PGI(2) infusion also attenuated postischemic leukocyte adhesion, which was significant by a 6-h prolonged administration (P0.05), but did not influence the increase of microvascular permeability. Both prostaglandins were unable to prevent the postischemic failure of capillary perfusion (no-reflow).Both prostaglandins did not significantly influence postischemic no-reflow phenomena, but appeared as potent inhibitors of reflow-paradox under the experimental circumstances of this study.